Beckwith-Wiedemann Syndrome via the CDKN1C Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 10005 | CDKN1C | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder characterized by macrosomia, macroglossia (large tongue), visceromegaly, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), omphalocele, neonatal hypoglycemia, ear creases/pits, adrenocortical cytomegaly, and renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly; Shuman et al. GeneReviews. 2010). BWS shows clinical heterogeneity and suspicion should arise if only a few of the clinical features are present. Individuals with BWS are also known to have somatic mosacism. For example, they can show hemihyperplasia. Early diagnosis is important, because children can have life threatening hypoglycemia and early-onset cancers. The prevalence of BWS is 1 in 13,700 livebirths (Choufani et al. American Journal of Medical Genetics Part C (Seminars in Medical Genetics)154C:343–354, 2010).
Genetics
Beckwith-Wiedemann syndrome is caused by defects in imprinting at the chromosomal location 11p15. Approximately 50% of BWS cases are the result of loss of maternal methylation, 20% due to paternal uniparental disomy, and 5% are the result of an imprinting center variant on the maternal chromosomal location 11p15. In addition, variants in CDKN1C can be found in 40% of familial BWS cases and 5-10% of sporadic BWS cases. CDKN1C, a putative tumor suppressor gene that negatively regulates cellular proliferation and a putative negative regulator of fetal growth, is a maternally expressed gene (Choufani et al. American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 154C:343–354, 2010). Variants in CDKN1C are inherited in an autosomal dominant manner. Most variants reported to date include missense variants; however, nonsense, missense, splice site, small insertions and deletions, and large duplications have also been described.
Clinical Sensitivity - Sequencing with CNV PG-Select
CDKN1C variants can be found in 40% of familial BWS cases and 5-10% of non-familial BWS cases. This sequencing test will not detect any imprinting defects that cause BWS.
Testing Strategy
This test provides full coverage of all coding exons of the CDKN1C gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for this test include patients suspected to have Beckwith-Wiedemann syndrome who have no methylation defects at chromosome 11p15 or individuals who have a family history of Beckwith-Wiedemann syndrome. Individuals who have BWS with cleft palate or neuroblastoma are also known to have CDKN1C variants (Li et al. Genomics 74:370–6, 2001; Alsultan et al. Pediatr Blood Cancer 51:695–8 2008). CDKN1C variants have also recently been reported in patients with IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies), which is an undergrowth developmental disorder (Arboleda et al. Nat Genet 2012 May 27. doi: 10.1038/ng.2275). This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.
Candidates for this test include patients suspected to have Beckwith-Wiedemann syndrome who have no methylation defects at chromosome 11p15 or individuals who have a family history of Beckwith-Wiedemann syndrome. Individuals who have BWS with cleft palate or neuroblastoma are also known to have CDKN1C variants (Li et al. Genomics 74:370–6, 2001; Alsultan et al. Pediatr Blood Cancer 51:695–8 2008). CDKN1C variants have also recently been reported in patients with IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies), which is an undergrowth developmental disorder (Arboleda et al. Nat Genet 2012 May 27. doi: 10.1038/ng.2275). This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| CDKN1C | 600856 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Beckwith-Wiedemann Syndrome | AD | 130650 |
Citations
- Alsultan et al. (2008). "Simultaneous occurrence of right adrenocortical tumor and left adrenal neuroblastoma in an infant with Beckwith-Wiedemann syndrome.." Pediatr Blood Cancer 51:695–8. PubMed ID: 18668518
- Arboleda et al. (2012). "Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome." Nat Genet May 27. doi: 10.1038/ng.2275. PubMed ID: 22634751
- Choufani et al. (2010). "Beckwith-Wiedemann syndrome.." American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 154C:343–354. PubMed ID: 20803657
- Li et al. (2001). "Imprinting status of 11p15 genes in Beckwith-Wiedemann syndrome patients with CDKN1C mutations.." Genomics 74:370–6. PubMed ID: 11414765
- Shuman et al. GeneReviews. 2010
- Shuman et al. GeneReviews. 2010
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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ORDER OPTIONS
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